The purpose of this revised R21 exploratory grant to NCCAM in response to PAR-03-153 is to extend the PI's previous human olfactory psychophysiology research and develop a quantitative electroencephalographic (qEEG) bioassay for registration of individually active (salient) versus inactive homeopathic remedies or placebo. Homeopathy's founder, Samuel Hahnemann MD, originally proposed olfactory sniffing as a valid route for clinical remedy administration. Convergent basic science evidence suggests that succussion (vigorous shaking) in the preparation of homeopathic remedies from animal, mineral, and plant sources, may persistently modify the physical structure of solvent to generate order, i.e., a unique informational signal, even in ultra-diluted solutions beyond Avogadro's number. Torres and Ruiz (1996) proposed that stochastic resonance in sensory systems is a model for optimizing detection of a weak signal (homeopathic remedy information) by addition of noise (succussions). No previous research has directly examined the effects in human populations of a given remedy dilution prepared with different numbers of succussions. Specific aims for the study are: I. To evaluate the feasibility of using acute evoked responses in quantitative electroencephalography (qEEG) alpha power during olfactory administration to detect the presence of a single homeopathic remedy (Sulphur) at different numbers of succussions per dilution step, prepared at a given dilution; II. To determine the feasibility of using the magnitude of acute evoked responses in quantitative electroencephalography (qEEG) alpha power during olfactory administration to detect the presence of a single homeopathic remedy at two different homeopathic serial dilution factors (prepared with a given number of succussions per dilution step); III. To evaluate the generalizability of findings for a separate polycrest remedy (Pulsatilla). Subjects will be N=108 (n=54/remedy) young adult volunteers with moderate (not excellent global health) prescreened for potential remedy salience of either Sulphur or Pulsatilla and tested in a two-phase study (one remedy per phase). Each participant will undergo pre-screening with the Homeopathic Constitutional Type Questionnaire for high criterion scores for symptoms of one of the two test remedies, followed by three laboratory sessions spaced one week apart (dilution sequence subject allocation balanced within each remedy type for 6c, 12c, and 30c potencies). Each session will involve eight presentations within a complete block design of randomized double-blind, placebo- controlled (both succussed remedy-free solvent and succussed plain distilled water) olfactory sniff tests (using time-locked sniff-EEG recordings via an airflow pressure transducer), using a given remedy dilution prepared with stirring only, 10, 20, or 30 succussions. The present study fills a major need in homeopathic clinical research to explore and understand remedy-related and remedy-person interactive factors that could contribute to well-known problems in replicability. Findings from this and follow- up studies via subsequent R01s could improve standardization of homeopathic remedy manufacturing and prescribing used in patient care and thereby advance the quality of clinical treatments and research for this leading form of complementary and alternative medicine worldwide. [unreadable] [unreadable] [unreadable]